Latent class analysis of ADHD and comorbid symptoms in a population sampleof adolescent female twins

Attention-deficit/hyperactivity disorder (ADHD) is a phenotypically heterog eneous and highly heritable syndrome, which commonly co-occurs with other p sychiatry disorders. To assess the role of genetic influences in ADHD, we u sed latent class analysis (LCA) to identify subtypes of ADHD taking into ac count its comorbidity with separation anxiety, oppositional defiant disorde r (ODD), and three major depression symptoms. A structured interview was us ed to collect diagnostic data from a population sample of 2904 adolescent f emale twins and their parents. LCA was applied to ADHD, separation anxiety, ODD symptom profiles obtained from the twins' parents, and major depressio n symptom profiles obtained from the twins' self-report. Odds ratios were u sed to test for familiality of class membership by examining the effect of zygosity on twin concordance within and between latent classes. Structural equation modeling was used to compute heritabilities for latent class membe rship. LCA revealed three ADHD categories of clinical interest: an inattent ive subtype without comorbidity, a second inattentive subtype with increase d number of ODD symptoms, and a combined inattentive/hyperactive-impulsive type with elevated levels of ODD, separation anxiety, and depressive sympto ms. LCA also distinguished an ODD class and a separation anxiety class, eac h without increased levels of other comorbid symptoms; a second ODD class c o-occurring with increased separation anxiety and depression symptoms; and a pure depression class. Odds ratios for MZ contrasted with DZ twin concord ance for individual latent class membership ranged from 2.5 to 19.4. Overal l, 66 % of MZ pairs, but only 36 % of DZ pairs, were assigned to the same l atent class, consistent with a genetic hypothesis for latent class membersh ip. Individual class membership was shown to have high heritability ranging from .34-.85. The pattern of latent classes suggested that in the general female adolescent population, there are three highly heritable ADHD subtype s, two of which are comorbid with other disorders. These classes were consi stent with a genetic hypothesis for ADHD, with each class potentially refle cting a unique genetic subtype.